1 research outputs found
Aldehyde Recognition and Discrimination by Mammalian Odorant Receptors via Functional Group-Specific Hydration Chemistry
The mammalian odorant
receptors (ORs) form a chemical-detecting
interface between the atmosphere and the nervous system. This large
gene family is composed of hundreds of membrane proteins predicted
to form as many unique small molecule binding niches within their
G-protein coupled receptor (GPCR) framework, but very little is known
about the molecular recognition strategies they use to bind and discriminate
between small molecule odorants. Using rationally designed synthetic
analogs of a typical aliphatic aldehyde, we report evidence that among
the ORs showing specificity for the aldehyde functional group, a significant
percentage detect the aldehyde through its ability to react with water
to form a 1,1-<i>geminal</i> (<i>gem</i>)-diol.
Evidence is presented indicating that the rat OR-I7, an often-studied
and modeled OR known to require the aldehyde function of octanal for
activation, is likely one of the <i>gem</i>-diol activated
receptors. A homology model based on an activated GPCR X-ray structure
provides a structural hypothesis for activation of OR-I7 by the <i>gem</i>-diol of octanal